Inhibition of erythropoietin-producing hepatoma receptor B4 (EphB4) signalling suppresses the vascularisation and growth of endometriotic lesions
Background purpose: The introduction of endometriotic lesions is crucially determined by the development of recent bloodstream vessels. In our study, we analysed whether this method is controlled by erythropoietin-producing hepatoma receptor B4 (EphB4) signalling.
Experimental approach: We first assessed the anti-angiogenic action from the EphB4 inhibitor NVP-BHG712 in various in vitro angiogenesis assays. Then, endometriotic lesions were surgically caused within the dorsal skinfold chamber and peritoneal cavity of NVP-BHG712- or vehicle-treated BALB/c rodents. This permitted to review the result of EphB4 inhibition on their own vascularisation and growth by way of intravital fluorescence microscopy, high-resolution ultrasound imaging, histology and immunohistochemistry.
Key results: Non-cytotoxic doses of NVP-BHG712 covered up the migration, tube formation and sprouting activity of both human dermal microvascular endothelial cells (HDMEC) and mouse aortic rings. Accordingly, we detected a lesser circulation system density in NVP-BHG712-treated endometriotic lesions. It was connected having a reduced lesion growth as a result of considerably lower quantity of proliferating stromal cells in comparison with vehicle-treated controls.
Conclusions and implications: Inhibition of EphB4 signalling suppresses the vascularisation and development of endometriotic lesions. Hence, EphB4 represents an encouraging medicinal target to treat endometriosis.